Journal
FRONTIERS IN ONCOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2021.777867
Keywords
breast cancer; MDM2; CDK4; 6 inhibitor; estrogen receptor; endocrine resistance
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Funding
- National Breast Cancer Foundation [EC17-002]
- Love Your Sister Foundation
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This review explores the role of the p53/MDM2 axis in the treatment of ER+ breast cancer and the potential of targeting p53/MDM2 by inhibiting MDM2 in the setting of CDK4/6i resistance.
With the adoption of inhibitors of cyclin dependent kinases 4 and 6 (CDK4/6i) in combination with endocrine therapy as standard of care for the treatment of advanced and metastatic estrogen receptor positive (ER+) breast cancer, the search is now on for novel therapeutic options to manage the disease after the inevitable development of resistance to CDK4/6i. In this review we will consider the integral role that the p53/MDM2 axis plays in the interactions between CDK4/6, ER alpha, and inhibitors of these molecules, the current preclinical evidence for the efficacy of MDM2 inhibitors in ER+ breast cancer, and discuss the possibility of targeting the p53/MDM2 via inhibition of MDM2 in the CDK4/6i resistance setting.
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